Pancreatic Islets

Pancreatic Islets: Almost 80 years ago, Dr. Frederick Banting published a report about use of pancreatic Islets to treat diabetes. He obtained those Islets from the pancreas of a dog. By first tying-off that pancreas, he eliminated the digestive enzymes that would otherwise have destroyed the insulin in the Islets.

Following the publication of that report, diabetics could hope for a way to replace the insulin lacking in their system. Biochemists were able to extract insulin from the pancreas of an animal. That insulin could then be prepared for injection into a diabetic patient. At that time, doctors could only dream about transplanting Islet cells into a diabetic patient.

Doctors have since learned that the Islets contain several types of cells. Among those various Islets cells, only the beta cells have the ability to make insulin. In the 1970s, a group of medical researchers began to look for a way to transplant beta cells into diabetic patients. Gradually, their research produced significant results.

Dr. Bernard Hering at the University of Minnesota transplanted Islets cells from pigs into monkeys. He published a report about that transplantation in Nature Magazine. Then in June of 2000, the world of medicine learned about a more advanced type of Islet transplantation. Doctors at the University of Alberto in Edmonton, Canada had transplanted Islets cells into human diabetic patients.

The Canadian doctors published the details of their transplantation in The New England Journal of Medicine. They followed that initial report with other reports about the ability of the transplanted Islets to maintain production of insulin. Those follow-up reports indicated that 10% of the 65 patients given the transplanted Islets remained free of a need for insulin five years later (in 2005).

The follow-up report included some other important information. A number of the patients who had received the transplanted Islets found that even though they later needed to receive insulin, they did not need as much insulin as they had prior to the transplantation. Moreover, those patients who had to resume their use of insulin found that after the transplantation they were able to maintain a more stable glucose level.

Among the patients who had received the transplanted Islets, doctors observed something that related to another problem, a problem that challenges many diabetics. Often a patient with diabetes develops what is known as “hypoglycemia unawareness.” When a diabetic develops that condition, he or she can not detect evidence that his or her body needs sugar. Symptoms of “hypoglycemia unawareness” declined among those patients who had received the transplanted Islets.

After medical doctors learned about the results of the Canadian experiment, they studied carefully the procedures used by those Canadian doctors. A number of doctors wanted to replicate the experiment conducted at the University of Alberto. Doctors who hoped to repeat that experiment learned that they needed to follow the following procedure.

The Canadian doctors had taken Islets cells from deceased organ donors. They had prevented destruction of the beta cells by using special enzymes during the removal of the Islets cells. They had then purified and processed those beta cells. Those purified and processed cells were given to a radiologist.

The radiologist used both X-rays and ultra sound to guide a plastic tube through the upper abdomen of the patient who was to receive the transplanted Islet cells. Once safely through the abdomen of that patient, the plastic tube was inserted in the patient’s portal vein (a vein from the liver). The radiologist then infused the Islets cells into the tranquilized patient.

The radiologist did not infuse just a couple cells into each patient. Doctors had determined the number of Islets “equivalents” needed by each patient who was supposed to get some transplanted Islets cells. The doctors had based their determination on the patient’s body weight. The Canadian doctors had found that a diabetic needs 10,000 Islets “equivalents” for every kilogram in his or her body weight.

Following the performance of such a procedure, doctors could expect the transplanted Islets cells to produce insulin for a at least 14 days. There were, as shown by the data in the published report, some patients who produced insulin for far longer than that short, 14 day period. Doctors have initiated a look at ways to refine the procedure used in Canada.

One refinement that has been presented to some medical professionals employs changes in the nature of the material infused into the patient. Doctors who tested this particular refinement put a special coating on the processed and infused Islet cells. Patients who received an infusion of Islets cells with the new coating experienced fewer side effects.

Prior to introduction of this new refinement, some patients had complained about mouth sores, GI problems, and increased infections. The physicians treating the patients with the Islets transplants had seen increases in the patients’ blood pressure and blood cholesterol. None of those side effects could be found among patients who got Islets cells with the new type of coating.

While some medical researchers have focused on delivery of the infused Islet cells, others have looked at how to improve patients’ acceptance of those cells. As in any transplantation, the transplantation of Islet cells demands the use of immunosuppressive drugs. Those drugs put limits on the body’s natural tendency to attack any foreign material within the body.

The Canadian doctors did not rely on the conventional immunosuppressive drugs when doing their Islets cells transplants. They used new drugs, drugs that proved able to enhance the patients’ acceptance of the transplanted cells. They administered those drugs according to a carefully selected pattern.

One drug, doclimszumab, was given to each patient by IV. The patient received that drug immediately after completion of the transplantation. The administration of that drug was brief; the patient did not need to be hooked to the IV for a lengthy amount of time.

Upon discontinuation of the doclimszumab, the patient received two other immunosuppressive drugs—sirulimus and tociclimus. The patient needed to continue taking those drugs for as long as the transplanted Islets cells produced a satisfactory amount of insulin.